PROJECT(SUMMARY( ! Peptide therapeutics combine high potency and selectivity, and engender fewer side effects than traditional small molecules. This has fueled interest in peptides filling the gap between `biologics' and small molecules as compounds that have key desired properties from both the other classes. There are however some challenges ? the major one being susceptibility to enzyme catalyzed hydrolytic cleavage and inactivation. We propose here a strategy targeted towards an important class of peptide ligands that have therapeutic value. Via chemical modification using rapid, high yielding reactions and through careful analysis of the key proteases involved in inactivation, we are able to generate large number of compounds that retain activities at their cognate receptor but are completely refractory to the frontline hydrolytic enzymes. At the end of Phase I studies, candidate peptides will be chosen to advance further. Because of the large number of derivatives possible, fine-tuning of the pharmacological properties is achieved in a short period of time. Our technology also provides an easily adaptable platform to the broader community to stabilize their own peptide templates for preclinical development.!